A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease

The Tohoku Journal of Experimental Medicine
Hidekazu Nishimura, Mutsuo Yamaya

Abstract

Ebola virus disease (EVD) has been a great concern worldwide because of its high mortality. EVD usually manifests with fever, diarrhea and vomiting, as well as disseminated intravascular coagulation (DIC). To date, there is neither a licensed Ebola vaccine nor a promising therapeutic agent, although clinical trials are ongoing. For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. Thus, the proteases have been considered as potential targets for drugs against EVD. However, no protease inhibitor has been presented as effective clinical drug against it. A synthetic serine protease inhibitor, nafamostat mesilate (NM), reduced the release of CatB from the rat pancreas. Furthermore, it has anticoagulant activities, such as inhibition of the factor VIIa complex, and has been used for treating DIC in Japan. Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. Moreover, the drug has a history of large-scale production and clinical use, and the i...Continue Reading

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Citations

Jun 20, 2020·Journal of Thrombosis and Haemostasis : JTH·Toshiaki IbaJecko Thachil
Aug 28, 2018·Frontiers in Immunology·Kuldeep DhamaWanpen Chaicumpa
Jul 1, 2020·Neural Regeneration Research·George Zaki Ghali, Michael George Zaki Ghali
Dec 4, 2020·World Journal of Clinical Cases·Masaki OkajimaHideyuki Mouri
Apr 22, 2020·The Journal of Infection·Huilan TuJifang Sheng
Feb 23, 2021·Journal of Molecular Structure·Deep BhowmikDiwakar Kumar
Oct 10, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Mansab Ali SaleemiEng Hwa Wong
Nov 18, 2020·Respiratory Medicine·Mukta AgrawalAmit Alexander

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